Smoking is the leading preventable cause of cancer mortality in the US, making improved smoking treatment a vital public health goal. However, most smokers trying to quit ultimately relapse, and little is known about how to treat them. This project is designed to identify highly effective intervention components for recently relapsed smokers that can be included in a chronic care treatment for smoking that comprises effective intervention components for every phase of smoking treatment and that is feasible for use in healthcare settings. Participants from Project 3 of this POI application (the Cessation RCT) who relapse will transition to this Relapse Recovery project (N~776). Three intervention factors (each comparing an enhanced intervention component with a standard one) will be tested using a factorial Sequential Multiple Assignment Randomized Trial (SMART) design. All participants will be randomized to a Preparation factor comparing two strategies for preparing relapsers to requit. However, only participants choosing to make a new quit attempt will be randomized to the two Cessation factors: 1) Personalized vs. Regular Cessation Medication, and 2) Front-loaded vs. Regular Cessation Counseling. The enhanced Preparation and Cessation intervention components are designed to address the major challenges facing relapsers. The enhanced Preparation component (Smoking Reduction Counseling) is designed to counter demoralization and reduce tobacco dependence. Personalized Cessation Medication is designed to increase medication adherence and reduce withdrawal craving during a quit attempt, while Front-loaded Cessation Counseling is designed to reduce early lapsing by providing support and skills training early in the quit attempt. Analyses will determine the main and interactive effects of the two Cessation factors on smoking abstinence and determine whether these effects differ as a function of the Preparation factor. Analyses will also determine the effects of the Preparation factor on the likelihood of a meaningful quit attempt. The proposed research will be the first comparative effectiveness research to evaluate novel but promising Relapse Recovery intervention components in healthcare settings thus facilitating their rapid translation to real-world use.